Synthesis of an "all-in-one" nanotherapeutic platform for triple-amplification chemodynamic therapy of osteosarcoma

Abstract

High recurrence rates after surgery and unacceptable side effects of chemotherapy and radiotherapy are challenges in the treatment of osteosarcoma (OS). Therefore, the development of nanoplatforms with combined tumor inhibition efficiency and fewer side effects is a promising strategy for the treatment of OS. In this paper, a biocompatible therapeutic nanoplatform (Fe-Zr@PDA@GOx) was constructed with a simple and efficient strategy for the treatment of OS. First, as an excellent Fenton reaction reagent, iron ions in the nanoplatform can generate highly toxic hydroxyl radicals (•OH) with hydrogen peroxide (H2O2) in the tumor microenvironment and induce tumor cell death. Then, the modification of polydopamine endows the nanoplatform with photothermal responsiveness, with a photothermal conversion efficiency of 28.0%. Importantly, the conversed heat by polydopamine both promotes the release of glucose oxidase (GOx) and increases the rate of the Fenton reaction. Furthermore, GOx-mediated starvation treatment (SDT) can also provide suitable reaction conditions and sufficient H2O2 to realize the amplification of chemodynamic therapy (CDT). Finally, the doping of Zr ions can interact with Fe to form dual active centers in the Fenton reaction and further accelerate the generation of •OH. Both in vitro and in vivo experiments reveal the synergistic photothermal/CDT/SDT anti-tumor effect. Therefore, this work provides an effective strategy for the treatment of OS.